Inhibitory effect of polysaccharides isolated from Angelica sinensis on hepcidin expression

J Ethnopharmacol. 2011 Apr 12;134(3):944-8. doi: 10.1016/j.jep.2011.02.015. Epub 2011 Feb 17.

Abstract

Ethnopharmacological relevance: Angelica sinensis polysaccharide is an important bioactive component of Angelica sinensis (Oliv.) Diels that has been used in traditional Chinese medicine for treating gynecological disorders and anemia.

Aim of the study: Previous study indicated that Angelica sinensis polysaccharide (ASP) may promote plasma iron levels by suppressing the expression of hepcidin, a negative regulator of body iron metabolism, in the liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin expression as well as the involved mechanisms.

Materials and methods: ASP (1g/kg) or vehicle (normal saline) was intragastrically administrated to rats everyday for 14 d. Intraperitoneal injections of recombinant human erythropoietin (rhEPO, 2000 U/kg) were given to positive control group. Erythropoietin and hepcidin levels in serum at different time points were determined by enzyme-linked immunosorbent assay. Western blot was used to investigate the expression of 6 pertinent signal proteins in liver.

Results: ASP significantly reduced hepcidin expression by inhibiting the expression of signal transducer and activator of transcription 3/5 (STAT3/5) and mothers against decapentaplegic protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which further down-regulated hepcidin by repressing CCAAT/enhancer-binding protein α (C/EBPα), SMAD4, and the phosphorylation process of STAT3/5.

Conclusions: ASP can suppress the expression of hepcidin in normal rats, and may be used in the treatments of hepcidin-induced diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelica sinensis / chemistry*
  • Animals
  • Antimicrobial Cationic Peptides / metabolism*
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Erythropoietin / biosynthesis
  • Hepcidins
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • STAT Transcription Factors / metabolism
  • Smad4 Protein / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • CCAAT-Enhancer-Binding Protein-alpha
  • HAMP protein, human
  • Hamp protein, rat
  • Hepcidins
  • Polysaccharides
  • STAT Transcription Factors
  • Smad4 Protein
  • Smad4 protein, rat
  • Erythropoietin